Description
Jean Bennett, Katherine A. High and Albert Maguire shared the 2026 Breakthrough Prize in Life Sciences. This prize recognizes work that led to the first FDA–approved gene replacement therapy. It has transformed the lives of people born with Leber congenital amaurosis, a rare inherited retinal disease that usually results in total blindness in early adulthood, enabling children who had been going blind to gain their independence, attend regular schools, play outside at night, and in some cases even qualify for driver’s licenses. The therapy replaces the defective RPE65 gene, which produces a malfunctioning version of a protein critical to the visual cycle – the process by which the retina responds to light. The husband-and-wife team of molecular biologist Bennett and ophthalmic surgeon Maguire invented and developed the therapy from first conception to an effective treatment in animal models (including restoring sight to a number of Swedish Briard dogs which they went on to adopt). In 2005, High, a physician-scientist at Children’s Hospital of Philadelphia (CHOP) invited Bennett and Maguire to collaborate on a human trial. High’s laboratory and clinical gene therapy expertise proved crucial in the development of the approved drug, including gaining regulatory approval to conduct the initial clinical trials, and in directing the production and characterization of high-quality viral vector preparations used to introduce the replacement gene. The three physician-scientists worked together to design the pivotal trial, including developing and validating a novel clinical endpoint to measure the vector’s clinical effect.
Watch Gigi Hadid and Tekedra Mawakana award the Breakthrough Prize to Bennett, High, and Maguire: https://youtu.be/wNv71qkfzGo?si=2gp4jzXIeBueAQD1
Nearly all eligible Leber congenital amaurosis patients with RPE65 mutations in the United States have now been treated, and many others around the world are now gaining access to the therapy. The benefits have proved durable, with patients treated over a decade ago maintaining stable vision improvements. More broadly, this discovery demonstrated that the technology could work safely and effectively, establishing regulatory pathways and manufacturing approaches that opened the door to gene therapy approvals for a range of genetic diseases. Since their pioneering work, hundreds of trials, including over 100 retinal gene therapy trials have been conducted, with more than half a dozen currently in late-stage clinical testing.